This proposal describes a binding protein design that merges important antibody combining site features with a protein framework that is robust. Antibodies generally have rather low stabilities due to the often weak association of the light and heavy chain variable domains that together, form the antigen combining site. This stability problem is accentuated in recombinant antibodies, which are engineered for production in prokaryotes by deletion of constant region domains. Despite simplification of their molecular architecture, recombinant antibodies often fold very inefficiently in bacteria, presumably due to their dimeric structure and eukaryotic origin. The proposed binding protein design utilizes a framework based on a single protein domain from a thermophilic enzyme of prokaryotic origin. Not only is this expected to endow the proposed binding proteins with a high degree of stability, but it should also facilitate efficient expression in E.coli. The proposed binding protein design will achieve these enhanced structural features without compromising binding site character. The arrangement and number of complementary determining region-like loops is similar to that of antibodies and thus these binding proteins are expected to achieve high affinity and specificity through a wide diversity of combining site geometries. PROPOSED COMMERCIAL APPLICATION: The diversity of antibody binding specificities makes them useful in an immense variety of applications. The proposed binding-proteins are also expected to have this powerful property, but with the added benefits of efficient expression in E.coli, high stability, small size and a potential for affinities that are higher than that normally seen in antibodies.